Magnetized algae catalyst by endogenous N to effectively trigger peroxodisulfate activation for ultrafast degraded sulfathiazole: Radical evolution and electron transfer.

An innovative Fe-N co-coupled catalyst MN-2 was prepared from waste spirulina by co-pyrolysis as a highly active carbon-based catalyst for the activation of peroxydisulfate (PDS) for the degradation of sulfathiazole (ST). The protein-rich raw material Spirulina provided sufficient N during the pyrolysis process, thus achieving N doping without an additional nitrogen source, optimizing the interlayer structure of the biochar material and effectively inhibiting the leaching of the ligand metal Fe. MN-2 showed highly efficient catalytic activity for peroxydisulfate (PDS), with a degradation efficiency of 100% for ST within 30 min and a kinetic constant (kobs) reached 0.306 min-1, benefiting from the excellent adsorption ability of MN-2 forming MN-2-PDS* complexes and the electron transfer process generated by Fe3+ and Fe2+ cycling, oxygen-containing functional groups. The effects of PDS dosage, initial pH and coexisting anions on the oxidation process were also investigated. Free radical quenching, electron paramagnetic resonance and electrochemical measurements were employed to explain the hydroxyl (·OH) and sulfate (SO4·-) as the dominant active species and the electron transfer effect on the removal of ST. MN-2 maintained a ST removal rate of 84% after four recycling experiments, showing a high reusability performance. This work provides a simple way to prepare magnetized N-doped biochar, a novel catalyst (MN-2) for efficient activation of PDS for ST degradation, and a feasible method for removing sulfanilamide antibiotics in water environment.

Efficient Adsorption of a Sulfonamide Antibiotic in Aqueous Solutions with N-doped Magnetic Biochar: Performance, Mechanism, and Reusability.

Conventional biochar has limited effectiveness in the adsorption of sulfonamide antibiotics, while modified biochar exhibits greater adsorption potential. Residues of sulfamethoxazole (SMX) in the aquatic environment can threaten the safety of microbial populations as well as humans. In this study, iron-nitrogen co-doped modified biochar (Fe-N-BC) was prepared from palm fibers and doped with Fe and urea via synthesis at 500 °C. Fe-N-BC has a richer surface functional group based on elemental content, X-ray photoelectron spectroscopy, X-ray diffraction, and Fourier transform infrared spectroscopy. The Brunauer-Emmett-Teller (BET) specific surface area test exhibited Fe-N-BC, which possessed a greater surface area (318.203 m2/g) and a better developed pore structure (0.149 cm3/g). The results of the hysteresis loop and the Raman spectrum show that Fe-N-BC has a higher degree of magnetization and graphitization. Fe-N-BC showed a remarkable adsorption capacity for SMX (42.9 mg/g), which could maintain 93.4% adsorption effect after four cycles, and 82.8% adsorption capacity in simulated piggery wastewater. The adsorption mechanism involves pore filling, surface complexation, electrostatic interactions, hydrogen bonding, and π-π EDA interactions. The results of this study show that Fe-N-BC prepared from palm fibers can be a stable, excellent adsorbent for SMX removal from wastewater and has promise in terms of practical applications.

Daucosterol protects neurons against oxygen-glucose deprivation/reperfusion-mediated injury by activating IGF1 signaling pathway.

We previously reported that daucosterol (a sterolin) up-regulates the expression of insulin-like growth factor I (IGF1)(1) protein in neural stem cells. In this study, we investigated the effects of daucosterol on the survival of cultured cortical neurons after neurons were subjected to oxygen and glucose deprivation and simulated reperfusion (OGD/R)(2), and determined the corresponding molecular mechanism. The results showed that post-treatment of daucosterol significantly reduced neuronal loss, as well as apoptotic rate and caspase-3 activity, displaying the neuroprotective activity. We also found that daucosterol increased the expression level of IGF1 protein, diminished the down-regulation of p-AKT(3) and p-GSK-3ß(4), thus activating the AKT(5) signal pathway. Additionally, it diminished the down-regulation of the anti-apoptotic proteins Mcl-1(6) and Bcl-2(7), and decreased the expression level of the pro-apoptotic protein Bax(8), thus raising the ratio of Bcl-2/Bax. The neuroprotective effect of daucosterol was inhibited in the presence of picropodophyllin (PPP)(9), the inhibitor of insulin-like growth factor I receptors (IGF1R)(10). Our study provided information about daucosterol as an efficient and inexpensive neuroprotectants, to which the IGF1-like activity of daucosterol contributes. Daucosterol could be potentially developed as a medicine for ischemic stroke treatment.

Doxorubicin-mediated radiosensitivity in multicellular spheroids from a lung cancer cell line is enhanced by composite micelle encapsulation.

BACKGROUND: The purpose of this study is to evaluate the efficacy of composite doxorubicinloaded micelles for enhancing doxorubicin radiosensitivity in multicellular spheroids from a non-small cell lung cancer cell line. METHODS: A novel composite doxorubicin-loaded micelle consisting of polyethylene glycolpolycaprolactone/Pluronic P105 was developed, and carrier-mediated doxorubicin accumulation and release from multicellular spheroids was evaluated. We used confocal laser scanning microscopy and flow cytometry to study the accumulation and efflux of doxorubicin from A549 multicellular spheroids. Doxorubicin radiosensitization and the combined effects of irradiation and doxorubicin on cell migration and proliferation were compared for the different doxorubicin delivery systems. RESULTS: Confocal laser scanning microscopy and quantitative flow cytometry studies both verified that, for equivalent doxorubicin concentrations, composite doxorubicin-loaded micelles significantly enhanced cellular doxorubicin accumulation and inhibited doxorubicin release. Colony-forming assays demonstrated that composite doxorubicin-loaded micelles are radiosensitive, as shown by significantly reduced survival of cells treated by radiation + composite micelles compared with those treated with radiation + free doxorubicin or radiation alone. The multicellular spheroid migration area and growth ability verified higher radiosensitivity for the composite micelles loaded with doxorubicin than for free doxorubicin. CONCLUSION: Our composite doxorubicin-loaded micelle was demonstrated to have radiosensitization. Doxorubicin loading in the composite micelles significantly increased its cellular uptake, improved drug retention, and enhanced its antitumor effect relative to free doxorubicin, thereby providing a novel approach for treatment of cancer.

Quality of life and radiotherapy complications of Chinese nasopharyngeal carcinoma patients at different 3DCRT.

PURPOSE: the study aimed to compare the quality of life (QOL) and radiotherapy complications among Chinese nasopharyngeal carcinoma (NPC) patients at different 3-dimensional conformal radiotherapy (3DCRT) stages adjusting for other variables. METHODS: 511 NPC patients at different 3DCRT stages were enrolled. They were interviewed regarding SF-36, complications and socio-demographic variables and cancer- or treatment- related variables. Analysis of covariance (ANCOVA) based on SF-36, complications scores as dependent variables, 3DCRT stages as independent variables, and other variables as covariate were established. RESULTS: The influencing factors of PCS included 3DCRT stages and age group. The influencing factors of MCS included 3DCRT stages and income. Most QOL scores of NPC patients were significantly associated with 3DCRT stage, after accounting for other variables. QOL scores of the patients receiving 3DCRT were the lowest, QOL scores of people after 3DCRT gradually increased. PCS scores of people greater than 5 years after 3DCRT was improved to or even better than the level before 3DCRT. The complications with significantly different scores of patients at different 3DCRT status included xerostomia, throat ache, hypogeusia, caries, hearing loss, snuffles. CONCLUSIONS: Clinicians should pay more attention to older NPC patients and patients with lower income. When patients receive 3DCRT, measures should be taken to reduce radiation injury to improve the patients' QOL.

Doxorubicin-loaded PEG-PCL copolymer micelles enhance cytotoxicity and intracellular accumulation of doxorubicin in adriamycin-resistant tumor cells.

BACKGROUND: Multidrug resistance remains a major obstacle to successful cancer chemotherapy. Some chemical multidrug resistance inhibitors, such as ciclosporin and verapamil, have been reported to reverse resistance in tumor cells. However, the accompanying side effects have limited their clinical application. In this study, we have developed a novel drug delivery system, ie, a polyethyleneglycol-polycaprolactone (PEG-PCL) copolymer micelle encapsulating doxorubicin, in order to circumvent drug resistance in adriamycin-resistant K562 tumor cells. METHODS: Doxorubicin-loaded diblock copolymer PEG-PCL micelles were developed, and the physicochemical properties of these micelles, and accumulation and cytotoxicity of doxorubicin in adriamycin-resistant K562 tumor cells were studied. RESULTS: Doxorubicin-loaded micelles were prepared using a solvent evaporation method with a diameter of 36 nm and a zeta potential of +13.8 mV. The entrapment efficiency of doxorubicin was 48.6% ± 2.3%. The micelles showed sustained release, increased uptake, and cellular cytotoxicity, as well as decreased efflux of doxorubicin in adriamycin-resistant K562 tumor cells. CONCLUSION: This study suggests that PEG-PCL micelles have the potential to reverse multidrug resistance in tumor cells.

Molecular mechanism study of chemosensitization of doxorubicin-resistant human myelogenous leukemia cells induced by a composite polymer micelle.

The present study was aimed to overcome the multidrug resistance (MDR) of tumor cells which accounts for the failure of clinical chemotherapy. A novel doxorubicin (DOX)-loaded composite micelle consisting of polyethylene glycol (PEG)-polycaprolactone (PCL)/Pluronic P105 has been developed and was proved to inhibit the drug resistance of human myelogenous leukemia (K562/ADR) cells. The modulation mechanism that DOX-loaded the composite micelle inhibited MDR was for the first time investigated at cell levels. Results indicated that the cytotoxicity in K562/ADR cells treated by DOX-loaded PEG-PCL/P105 composite micelle was about 4 times higher than DOX solution at 12 µg/mL of DOX. Confocal images showed that the DOX-loaded composite micelles gradually entered into cytoplasm and nucleus, and stayed in intracellular much longer than DOX solution. All the micelles (PEG-PCL micelle, P105 micelle and PEG-PCL/P105 composite micelle) did not change Pgp expression on the surface of K562/ADR cells. However, further study revealed that micelle containing of P105 (P105 or PEG-PCL/P105 composite micelle) significantly decreased ATP level, and consequently restricted the activity of Pgp by down-regulation of mitochondrial membrane potential. On the other hand, the PEG-PCL micelle had no effect on both mitochondrial membrane potential and ATP level of the K562/ADR cells, but its access to K562/ADR cells through endocytic pathway avoided the recognition of Pgp. The PEG-PCL/P105 composite micelle was designed based on the combination of P105-mediated down regulation of mitochondrial membrane potential the malignant cells and PEG-PCL-mediated internalization effect. Therefore, the novel composite micelle is a promising drug delivery system for anticancer drug to overcome MDR.

A novel method to predict protein-protein interactions based on the information of protein-protein interaction networks and protein sequence.

Protein-protein interactions (PPIs) are crucial to most biochemical processes in human beings. Although many human PPIs have been identified by experiments, the number is still limited compared to the available protein sequences of human organisms. Recently, many computational methods have been proposed to facilitate the recognition of novel human PPIs. However the existing methods only concentrated on the information of individual PPI, while the systematic characteristic of protein-protein interaction networks (PINs) was ignored. In this study, a new method was proposed by combining the global information of PINs and protein sequence information. Random forest (RF) algorithm was implemented to develop the prediction model, and a high accuracy of 91.88% was obtained. Furthermore, the RF model was tested using three independent datasets with good performances, suggesting that our method is a useful tool for identification of PPIs and investigation into PINs as well.

DOX-loaded PEG-PLGA and Pluronic copolymer composite micelles enhances cytotoxicity and the intracellular accumulation of drug in DOX-resistant tumor cells.

In the present study, doxorubicin (DOX) loaded polyethyleneglycol-poly (DL-lactic-co-glycolic acid) micelle as well as composite micelles composed polyethyleneglycol- poly(DL-lactic-co-glycolic acid) (PEG-PLGA) and Pluronic 105 (P105) were constructed. The micelles, with diameter around 106 nm and 85 nm respectively, were prepared by solvent evaporation method. The results showed that the encapsulation of DOX in micelles could significantly enhance its cytotoxicity in a DOX resistant tumor cell line, K562/DOX. The combination of PEG-PLGA and Pluronic further improved both the tumor-suppressive activity and the intracellular accumulation of DOX, indicating that the composite micelles would be potential to reverse the multidrug resistance in tumor cells.

[Progress in the study of micelle delivery system reversing multidrug resistance].

Multidrug resistance (MDR) of cancer cells to anti-tumor drugs remains a major impediment to successful chemotherapy. There has been an increasing interest in the studies of the mechanism and reverse of the MDR. Being a reliable and safe way to reverse MDR, drug delivery systems (DDS) such as micelle, liposome and nanoparticle, represent a promising prospect both in research and application in recent years. On the basis of recent studies, the effect and mechanism of micelles on reversing MDR are reviewed. And it is anticipated that DDS could contribute greatly to reversing MDR in the future.

A semi-supervised learning based method: Laplacian support vector machine used in diabetes disease diagnosis.

Pattern recognition methods could be of great help to disease diagnosis. In this study, a semi-supervised learning based method, Laplacian support vector machine (LapSVM), was used in diabetes diseases prediction. The diabetes disease dataset used in this article is Pima Indians diabetes dataset obtained from the UCI Repository of Machine Learning Databases and all patients in the dataset are females at least 21 years old of Pima Indian heritage. Firstly, LapSVM was trained as a fully-supervised learning classifier to predict diabetes dataset and 79.17% accuracy was obtained. Then, it was trained as a semi-supervised learning classifier and we got the prediction accuracy 82.29%. The obtained accuracy 82.29% is higher than other previous reports. The experiments led to the finding that LapSVM offers a very promising application, i.e., LapSVM can be used to solve a fully-supervised learning problem by solving a semi-supervised learning problem. The result suggests that LapSVM can be of great help to physicians in the process of diagnosing diabetes disease and it could be a very promising method in the situations where a lot of data are not class-labeled.

A novel camptothecin derivative incorporated in nano-carrier induced distinguished improvement in solubility, stability and anti-tumor activity both in vitro and in vivo.

PURPOSE: An oil/water nanoemulsion was developed in the present study to enhance the solubility, stability and anti-tumor activity of a novel 10-methoxy-9-nitrocamptothecin (MONCPT). MATERIALS AND METHODS: MONCPT nanoemulsion was prepared using Lipoid E80 and cremophor EL as main emulsifiers by microfluidization. The droplet size of the nanoemulsion was measured by dynamic light scattering. In vitro drug release was monitored by membrane dialysis. Kinetics of MONCPT transformed into carboxylic salt was performed in phosphate buffer at different pH. Hemolysis of MONCPT nanoemulsion was conducted in rabbit erythrocytes. Solubilization character of MONCPT in nanoemulsion was experimented using Nile red as a solvatochromic probe. In vitro cytotoxicity of the nanoemulsion was measured in A549 and S180 cells using Sulforhodamine B protein stain method, and suppression rate of tumor growth was investigated in S180-bearing mice. The cell cycle effects of MONCPT nanoemulsion on S180 cells were analyzed by flow cytometry. Distribution of the nanoemulsion in A549 cells and S180-bearing mice were also investigated by fluorescence image. RESULTS: MONCPT is incorporated in the nanoemulsion in form of lactone with concentration of 489 microg/ml, more than 200 folds higher than that in water. Experiments using Nile red as a solvatochromic probe indicated that more MONCPT might be located in the interfacial surfactant layer of the nanoemulsion than that in discrete oil droplet or continuous aqueous phase. Nanoemulsion could release MONCPT in a sustained way, and it was further shown to notably postpone the hydrolysis of MONCPT with longer hydrolysis half-life time (11.38 h) in nanoemulsion at pH 7.4 than that of MONCPT solution (4.03 h). No obvious hemolysis was caused by MOCPT nanoemulsion in rabbit erythrocytes. MONCPT nanoemulsion showed a marked increase in cytotoxic activity, 23.6 folds and 28.6 folds in S180 cells and A549 cells respectively via arresting the cell at G2 phase, compared to that induced by MONCPT injection. It correlated well to the in vivo anti-tumor activity of MONCPT nanoemulsion with suppression rate of 93.6%, while that of MONCPT injection was only 24.2% at the same dosage. Moreover, nanoemulsion exhibited enhanced capability of delivering drug into malignant cell's nucleus in vitro and induced drug accumulation in tumor in S180-bearing mice using in vivo imaging. CONCLUSION: The nanoemulsion prepared exhibited an improved MONCPT solubility, stability and anti-tumor activity, providing a promising carrier for cancer chemotherapy using MONCPT.